A possible link between low maternal levels of cholesterol and severe birth defects is the focus of a major new study, international researchers said yesterday.

Low cholesterol during pregnancy may interfere with the proper functioning of the so-called sonic hedgehog gene, potentially resulting in a massive brain abnormality, the International Genetics Conference in Melbourne was told.

Professor Max Muenke, head of the medical genetics branch of the National Human Genome Research Institute in the United States, said after his presentation that cholesterol deficiency was linked to a condition known as HPE, which affects one in every 250 embryos and one in 10,000 babies at birth.

HPE occurs when the brain fails to divide into two halves and is the most common anomaly of the developing brain. Ninety-nine per cent of affected embryos are spontaneously aborted and 90 per cent of live births die within a year.

Surviving babies suffer extreme mental retardation and most are unable to walk or talk.

Professor Muenke said the most important of the 10 genes linked to HPE was the sonic hedgehog, which also regulates growth of limbs, hands and feet.

However, the sonic hedgehog is dependent on cholesterol to function properly.

"Cholesterol comes into play in that sonic hedgehog . . . can only work properly when [this] protein is bound to cholesterol," Professor Muenke said.

A retrospective study involving 10,000 women had already started and another 10,000 would be enrolled for a study following them through pregnancy.

"Our hypothesis is that low maternal cholesterol is not good for the developing embryo," he said.

"To test that we want to look at large numbers of pregnant women and look at their cholesterol and see whether in those women who have low cholesterol, whether those babies have a defect in development."

Professor Muenke said studies had shown that rats given drugs to lower their cholesterol during pregnancy gave birth to pups with HPE.

He said there was no doubt that high cholesterol was bad in the long run, however questions remained about pregnancy.

"What we're trying to find out is what's the best cholesterol in pregnancy, and we don't know the answer to that."

Pregnant women are now advised against taking any cholesterol-lowering drugs because of the risk of HPE.